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Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.
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Objective:To investigate the mutation of proviral integration site for Moloney murine leukemia virus 1 (PIM1) in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:Paraffin-embedded tissues of 38 DLBCL patients surgically resected at Shiyan Taihe Hospital from January 2016 to March 2022 were collected. The mutation of PIM1 gene was detected by polymerase chain reaction (PCR)-Sanger sequencing. The DLBCL-related DUKE, DFCI and TCGA datasets in the cBioPortal database were screened to collect information on PIM1 gene mutation and expression and clinical prognosis. Patients were divided into PIM1 mutation-positive group and PIM1 mutation-negative group, and the differences in clinicopathological characteristics, tumor mutational burden (TMB), microsatellite instability (MSI) levels and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used for survival analysis, and univariate and multivariate survival analyses were performed using Cox proportional hazards model.Results:The PIM1 mutation rates of DLBCL patients in DUKE, DFCI, TCGA datasets and Shiyan Taihe Hosipital were 14.3% (96/673), 26.3% (26/99), 19.5%(8/41) and 28.9% (11/38), respectively, in which mutation site and mutation form were more commonly found in exon 4 and missense mutations. There were statistical differences in the PIM1 mutation rate among DLBCL patients with different age (DUKE dataset) and cell of origin (COO) classification (DFCI dataset) ( χ2 values were 8.22 and 4.40, both P<0.05). Compared with PIM1 mutation-negative group, the PIM1 mutation-positive group had a higher TMB in DUKE, DFCI and TCGA datasets (all P<0.05). In DUKE and DFCI datasets, the OS of PIM1 mutation-positive group was worse than that of PIM1 mutation-negative group (both P<0.05), and multivariate Cox regression analysis showed that PIM1 gene mutation-positive was an adverse prognostic factor of OS (DUKE dataset: HR = 1.661, 95% CI 1.151-2.396, P = 0.007; DFCI dataset: HR = 2.074, 95% CI 1.031-4.172, P =0.041). Conclusions:PIM1 gene mutation may be related to the poor prognosis of DLBCL patients.
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Objective: To investigate the correlation between the expression of p53, p63 or PIM1 protein and the survival of patients with nodal or extranodal diffuse large B-cell lymphoma (DLBCL). Methods: Immunohistochemical staining was applied to examine the expressions of p53, p63 and PIM1 proteins in nodal or extranodal DLBCL. The differences in the expressions of p53, p63 and PIM1 proteins between nodal and extranodal DLBCL were analyzed by χ2 test. Kaplan-Meier survival curve and COX proportional hazard model were used to analyze the relationship between the clinicopathological factors (including p53, p63 and PIM1 expressions) and the prognosis of patients with nodal or extranodal DLBCL. Results: Among 212 DLBCL cases, there were 101 nodal cases and 111 extranodal cases (including 55 cases of gastrointestinal DLBCL and 56 cases of non-gastrointestinal DLBCL). The expression rates of p53, p63 and PIM1 proteins in all cases were 19.0%, 25.2% and 54.7%, respectively. Among them, p53 was expressed more frequently in extranodal gastrointestinal cases (P 0.05). Much more p53-positive cases were observed with international prognostic index (IPI) ≥ 3 (P 0.05). Survival analysis showed that the expression of p53 or p63 protein was a significant inferior prognostic factor for overall survival (OS) and progression-free survival (PFS) in nodal patients or extranodal non-gastrointestinal DLBCL patients, respectively (both P < 0.05), while PIM1 expression was an inferior prognostic factor for PFS in extranodal gastrointestinal cases (P < 0.05). Conclusion: The molecular mechanisms of DLBCL pathogenesis may be different between different locations of DLBCL, which is worth further exploration.
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Objective:To explore the role of Pim-1 in the pathology of inflammatory bowel disease and the potential effect of Pim-1 inhibitor on treating such disease.Methods:Forty-five BALB/c mice were randomly divided into 5 groups (n=9):A normal control group,a inflammatory bowel disease group,two different dose of Pim-1 inhibitor treatment groups,and steroidhormone treatment group.The model of inflammatory bowel disease was induced by intracolonic administration of 2,4,6-trinitrobenzenestdfonic acid (TNBS) and ethanol mixture.Mice were treated with Pim-1 inhibitor [intraperitoneal inject,5 or 10 mg/(kg.d)] for 5 days and prednisone (intragastric administration,0.1 mg/d) for 5 days.The DAI,colon length,gross score and pathological grade were evaluated.The expressions ofT cell master transcription factors T-box expressed in T cells (T-bet),GATA binding protein 3 (GATA-3),RA orphan receptorγ (RORyt)and forkhead box P3 (Foxp3) were measured by Real-time PCR and Western blot,respectively.Results:Pim-1 inhibitor and prednisone showed therapeutic effect on acute TNBS colitis in vivo.GATA3 and RORγt were significantly up-regulated in acute TNBS colitis (P＜0.05).In contrast,the expression of Foxp3 was suppressed in the inflammatory bowel disease group,whereas it did not cause any significant change in T-bet expression (P＞0.05).Administration of Pim-1 inhibitor and prednisone resulted in suppression of GATA3,RORγt expression,and the increase of Foxp3 expression (P＜0.05).Administration of Pim-1 inhibitor and prednisone resulted in inhibition of T-bet mRNA expression (P＜0.05),but only prednisone could inhibit T-bet protein expression (P＞0.05).Conclusion:Pim-1 inhibitor significantly suppresses Th2-and Th17-type immune responses.Furthermore,Pim-1 inhibitor could induce T-cell differentiation towards a Treg phenotype.Pim-1 inhibitor has therapeutic effect on acute TNBS colitis.
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Objective To determine the expression of Pim-1 in hepatocellular carcinoma patients and its relationship with oncogene c-Myb.Methods From January 2009 to October 2013,136 patients with hepatocellular carcinoma (HCC) who were received surgical treatment at department of hepatobiliary surgery,the first affiliated hospital of the fourth military medical university,were selected to collect the clinical data,resected liver cancer tissues and para cancerous tissues,and complete the follow-up work.The patients were followed up by outpatient review or telephone.The deadline for follow-up was June 28,2017.To the end of the study,14 cases were lost,and 122 cases of HCC were included in this study.At the same time,85 cases of normal liver tissues which were obtained from hepatic hemangioma in the same period were collected as normal control group.The expression of Pim-1 and c-Myb protein detected in these liver tissues was detected by immuno-histochemical (IHC) staining.Western-blotting test was used to detect the expression of Pim-1 protein in human hepatoma cells SMMC-7721,HepG2,Hep3B,Huh7,MHCCL,MHCC-97H and normal human hepatocytes L-02,HL-7702.The average number of two samples was compared by Student's t test.The count data were analyzed by chi-square test or Spearman correlation analysis.Results The total positive expression rate of Pim-1 protein in liver cancer tissues was 88.5％ (108/122),which was significantly higher than that of para cancerous tissues 73.0％ (89/122) and normal liver tissues 69.4％ (59/85) (x2 =9.513,P =0.003;x2 =11.739,P =0.001).The total positive expression rate of c-Myb was 96 cases,of which 88 cases were positive for Pim-1 and c-Myb.Spearman correlation analysis showed that the expression of Pim-1 protein and c-Myb protein in HCC tissues was positively correlated (r =0.107,P =0.037).Compared with L-02 and HL-7702 cells,the content of Pim-1 in the cells of human hepatoma cells SMMC-7721,HepG2,Hep3B,Huh7,MHCCL,MHCC-97H increased significantly (P ＜0.01).Conclusions The expression level of Pim-1 in hepatocellular carcinoma tissues and hepatocellular carcinoma cells increased significantly,and it was correlated positively with the expression of proto oncogene c-Myb.This is closely related to the occurrence and development of HCC.
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Objective To study the expression of Pim1 protein in variant lesions of esophagus and its correlation with the clinicopathological parameters of esophageal cancer patients.Methods The esophageal biopsy specimens of 182 cases,including 37 cases of normal squamous epithelium,43 cases of low-grade intraepithelial neoplasia,31 cases of high-grade intraepithelial neoplasia,71 cases of esophageal squamous cell carcinoma were collected in the Third Affiliated Hospital of Xinxiang Medical University From January 2009 to March 2016.The expression of Pim1 protein in all esophageal tissues was detected by immunohistochemical method,and the correlation between Pim1 protein expression and clinicopathological parameters of esophageal squamous cell carcinoma patients was analyzed.Results The higher expression rate of Pim1 protein in esophageal normal squamous epithelium,low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and esophageal squamous cell carcinoma was 24.3％ (9/37),62.8 ％ (27/43),70.9％ (22/31),and 76.1％ (54/71),respectively.The higher expression rate of Pim1 protein in the tissue of low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and esophageal squamous cell carcinoma was significanlty higher than that in the esophageal normal squamous epithelium(x2 =11.89,14.79,26.70;P ＜ 0.05);there was no statistic difference of the higher expression rate of Pim1 protein in the tissue of low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia and esophageal squamous cell carcinoma (P ＜ 0.05).The expression of Pim1 protein was significantly positively correlated with lymph node metastasis and TNM stage(P ＜0.05),but not correlated with age and histological grade of patients (P ＜ 0.05).Conclusion The expression of Pim1 protein is closely related to the occurrence and development of esophageal cancer.
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Objective The aim of this study was to determine the expression of Pim-1 in primary hepatocellular carcinoma (PHC)and its clinical significance. Methods Immunohistochemical staining(IHC) was used to detect the expression of Pim-1 in 122 cases of PHC tissues,corresponding paracancer tissues,and 85 normal liver tissues. The relationship between the expression of Pim-1 protein and clinicopathological parameters was analyzed retrospectively. K-M method was used to analyze the effect of differ-ent Pim-1 expression on the survival time of PHC patients. Cox proportional hazard regression models were used to analyze risk fac-tors affecting survival time in patients with PHC. Results The total positive expression rate of Pim-1 protein in PHC tissues was 88. 5% ,which was significantly higher than that in adjacent tissues and normal liver tissues(P<0. 05). Univariate statistical analysis showed that patients with high expression of Pim-1 protein had poor preoperative liver function,more tumors,larger tumor diameter, high incidence of lymph node metastasis and high TNM stage(P<0. 05). Survival analysis suggested that the survival time of patients in the low expression group was significantly longer than that in the high expression of Pim-1 group(P<0. 05). Multivariate statisti-cal analysis showed that high expression of Pim-1 protein was an independent risk factor for survival time in patients with PHC(P<0. 001). Conclusion The expression level of Pim-1 in PHC tissues is significantly increased,which is related to the clinical pro-gress of PHC and the survival time of patients. Pim-1 overexpression indicates the poor prognosis of PHC patients.
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Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-β promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-β activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-β signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.
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Humans , Cells, Cultured , Gene Library , Interferon Type I , Metabolism , Interferon-beta , Genetics , Metabolism , Proto-Oncogene Proteins c-pim-1 , Genetics , Up-RegulationABSTRACT
AIM:To study the growth-inhibiting and proapoptotic effects of Pim-1 kinase inhibitor SMI-4a on human acute myeloid leukemia cell line U937.METHODS:The effect of SMI-4a on U937 cell viability was measured by CCK-8 assay.The apoptotic rate was assessed by flow cytometry with Annexin V-PI staining and by fluorescence microscopy with Hoechst 33342 staining.Methylcellulose was used to assess colony formation ability of the cells.The expression of β-catenin in the cell cytosol and nucleus was detected by Western blot,and the expression of apoptosis-related proteins in the U937 cells was also examined.Intracellular distribution of β-catenin was detected by the method of immunofluorescence.RESULTS:SMI-4a inhibited the viability of U937 cells.Annexin V-PI staining showed that SMI-4a induced apoptosis in dose-and time-dependent manners.Hoechst 33342 staining also verified the apoptosis.SMI-4a significantly inhibited the colony formation capacity of the U937 cells.The results of Western blot demonstrated that SMI-4a upregulated the expression of PARP and Bax,downregulated the expression of Bcl-2 and change the distribution of β-catenin in intracellular compartment.Immunofluorescence observation found that SMI-4a decreased the expression level of β-catenin in the U937 cells.CONCLUSION:SMI-4a induces U937 cell apoptosis through regulating the expression of apoptosis-related genes.
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AIM:To study the growth-inhibiting and proapoptotic effects of Pim-1 kinase inhibitor SMI-4a on human acute myeloid leukemia cell line U937.METHODS:The effect of SMI-4a on U937 cell viability was measured by CCK-8 assay.The apoptotic rate was assessed by flow cytometry with Annexin V-PI staining and by fluorescence microscopy with Hoechst 33342 staining.Methylcellulose was used to assess colony formation ability of the cells.The expression of β-catenin in the cell cytosol and nucleus was detected by Western blot,and the expression of apoptosis-related proteins in the U937 cells was also examined.Intracellular distribution of β-catenin was detected by the method of immunofluorescence.RESULTS:SMI-4a inhibited the viability of U937 cells.Annexin V-PI staining showed that SMI-4a induced apoptosis in dose-and time-dependent manners.Hoechst 33342 staining also verified the apoptosis.SMI-4a significantly inhibited the colony formation capacity of the U937 cells.The results of Western blot demonstrated that SMI-4a upregulated the expression of PARP and Bax,downregulated the expression of Bcl-2 and change the distribution of β-catenin in intracellular compartment.Immunofluorescence observation found that SMI-4a decreased the expression level of β-catenin in the U937 cells.CONCLUSION:SMI-4a induces U937 cell apoptosis through regulating the expression of apoptosis-related genes.
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Objective To study the effect of PIM-1 gene silence by RNA interference (RNAi) on the growth of human prostate cancer xenograft tumor in nude mice. Methods The xenograft tumor model of human prostate cancer was established by injecting PC-3 cells in armpits of 12 nude mice. After modeling, the nude mice were randomly divided into three groups: interference plasmid group (injecting with RNAi recombinant plasmid), empty plasmid group and negative control group (liposome every), 4 mice in each group. Mice were injected every 2 days for 5 times. The tumor volumes of xenografts were measured during experiment, and the curve of tumor growth was drawn accordingly. The quality of tumor was measured, and the inhibitory rate of tumor was calculated at the end of the experiments. The expression levels of PIM-1, c-MYC mRNA and protein in xenograft tumors were detected by real-time PCR and Western blot assay, respectively. Furthermore, immunohistochemistry staining was used to verify the expression of PIM-1. Results The xenograft tumor model of human prostate cancer was established successfully. The volume of tumor was significantly decreased 6 days after the injection treatment in interference plasmid group than that of empty plasmid group and negative control group. The effect of suppressing tumor growth was remarkable. The expression levels of PIM-1 mRNA and protein were down-regulated significantly in interference plasmid group than those of other two groups. The immunohistochemical staining of PIM-1 showed the same changes. There was no significant difference in c-MYC protein level between the three groups. But interestingly, the c-MYC mRNA level was significantly decreased in interference plasmid group than that of other two groups. Conclusion The silence of PIM-1 gene by RNAi recombinant plasmid can result a significant growth suppression of the human prostate cancer xenograft tumors in nude mice. The expression of c-MYC gene is down-regulated at translation level in the therapeutic group concomitantly. PIM-1 may be a promising target of gene therapy for prostate cancer.
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Objective: To construct a recombinant adeno-associated virus 2 vector (rAAV2-Pim-l) carrying rat proto-oncogene Pim-1, and to detect infected cell types and the expression of Pim-1 in rat retina infected by rAAV2-Pim-l. Methods: The pAOV-CAGMINI-EGFP-2A-MCS-3FLAG vector and Pim-1 PCR product were cleaved by Nhel enzyme. The recovered vector and target gene DNA were identified after agarose gel electrophores and linked to transformation, positive plasmid cloning and sequencing analysis. rAAV2-Pim-l expression plasmid pA0V-CAGMINI-EGFP-2A-Pim-l-3FLAG, packaging plasmid pAAV-RC and helper plasmid pHelper were co-transfected into 293 cells through using the Lipofectamine 2000, then high titer of rAAV2-Pim-l was purified. After rAAV2-Pim-l injection into rat intravitreal body, the infected retinal cell types were detected by immunofluorescence histochemistry staining; the expression of Pim-1 in the retina was quantified by Real-time PCR and Western blotting. Results: The construction of rAAV2-Pim-l plasmid was successful and the nucleotide sequence was right; Green fluorescence in 293 cells was found after plasmid transfection into 293 cells; The virus titer was 5.7 × 1015vg/L. After rAAV2-Pim-l infected rat retina in vivo, the infection percentage of retinal ganglion cells (RGCs) reached 71%, and a few of amacrine cells and hardly astrocytes were infected; the expression of Pim-1 mRNA and protein in the retina of rAAV2-Pim-l group was about 6. 61 times and 2. 29 times of the rAAV2-EGFP group respectively. Conclusion: rAAV2-Pim-l virus vector is successfully constructed and Pim-1 is overexpressed in the RGCs of infected rat retina.
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Objective To investigate the expression of Pim‐1 in non small cell lung cancer and adjacent normal tissues ,and study the relationship between c‐Myc and Pim‐1 in the corresponding tissue gene expression .Methods Totally 30 cases of non small cell lung cancer tissue and adjacent normal lung tissues were collected by surgical operation in department of thoracic surgery . Clinical data were statisticed and tracking late pathologic results ,using RT‐PCR ,qRT‐PCR and immunohistochemical method to de‐tect Pim‐1 mRNA ,c‐Myc and Pim‐1 protein expression in lung cancer and adjacent normal tissue ,and to analyze the relationship be‐tween the expression of Pim‐1 and c‐Myc .Results The positive rate of Pim‐1 mRNA and protein expression in non small cell lung cancer was obviously higher than that in adjacent normal tissue ,the mRNA expression levels were 0 .798 ± 0 .083 and 0 .394 ± 0 .107 (P0 .05) ,bue had related to ymph node metastasis and TNM stages of tumor (P<0 .05) ,with lymph node metastasis and TNM sta‐ges increases ,its expression quantity also rise .There was a positive correlation between Pim‐1 and c‐Myc protein expression ,corre‐lation coefficient (r) was 0 .433 (P=0 .017) .Conclusion High expression of Pim‐1 in non small cell lung cancer gene and is also increased with lymph node metastasis and TNM stages ,Pim‐1 and c‐Myc expression has positive correlation ,this could provide clues to the early diagnosis and prognosis evaluation of non small cell lung cancer ,and also provides a new train of thought and to find a new target for gene therapy of lung cancer .
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Objective: To investigate the antitumor effect of SGI-1776 on human ovarian cancer HO-8910 cells and its molecular mechanism. Methods: HO-8910 cells were cultured in vitro, and the proliferation inhibitory effects of SGI-1776 were determined by MTT assay and colony formation assay. The effect of SGI-1776 on the distribution of cell cycle phase was observed by flow cytometry with propidium iodide (PI) staining. hTe inhibition rate of migration and invasion were valued by transwell cell assay. Multiple molecular techniques, such as ELISA, Western blot, siRNA and cDNA transfection were used to explore the molecular mechanism. Results: SGI-1776 presented dramatic anti-tumor activity against HO-8910 cells in vitro, inhibited the cells proliferation and colony formation, and attenuated the migration and invasion in a dose-dependent manner, accompanied by cell cycle arrest in G1 phase. SGI-1776 caused the proliferation inhibition with concomitant decrease in Pim-1 kinase activity, down-regulated the expression of Pim-1 protein and and its downstream genes, such as CDK6, pCDK6, CDK4, pCDK4, CDK2 and pCDK2, and increased the expression of P21 and P27. Down-regulation expression of Pim-1 by siRNA followed SGI-1776 treatment resulted in enhanced cell proliferation inhibition rate and attenuated migration/invasion. Up-regulation of Pim-1 by cDNA transfection attenuated SGI-1776-induced cell proliferation inhibition and its migration/invasion. Conclusion: Pim-1 mediates the biological effect of SGI-1776 in human ovarian cancer HO-8910 cells, suggesting Pim-1 might be a novel target for human ovarian cancer.
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The overexpression of proto-oncogene protein c-pim-1 (Pim-1) in tumor tissue is related to the stage and prognosis.Recent studies indicate that Pim-1 plays a critical role in the proliferation and apoptosis of cells and the metastasis of tumor.Pim-1 acts as an essential factor in several signaling pathways and its expression and activation are regulated by many factors as well as affects others widely.As an influential factor in the occurrence and development of tumor,Pim-1 has been a potential target in oncotherapy.
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ObjectiveTo investigate the expression and biological significance of PIM1 in the breast cancer,atypical hyperplasia breast,and normal breast tissues.MethodsThe protein expression levels of PIM1 in the breast cancer,atypical hyperplasia breast,and normal breast tissues were assayed by immunohistochemistry and Western blot.ResultsThe expression rates of PIM1 protein were 78.75％ (63/80)in breast cancers,42.00％ (21/50) in atypical hyperplasia tissues,and 23.33 ％ (7/30) in normal breast tissues,respectively.A significant correlation was found between PIM1 expression and the clinical stage and lymphonodus metastasis.However,no significant correlation was found between PIM1 expression and patients'age and tumor sizes.The level of PIM1 protein in breast cancers was obviously higher than that in non - cancerous tissues.ConclusionsThe positive rate of PIM1 in breast cancers is significantly higher than that in atypical hyperplasia breast tissues and in normal breast tissues.PIM1 may be an early molecularevent in mammary tumorigenesis,and its overexpression may significantly relate to the malignant progression.It would be a new parameter for the early diagnosis and a biomarker for breast cancers.It is feasible to utilize paraffin specimens for index test with advantages of convenience,easy availability,and low expense.
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PURPOSE: The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population. MATERIALS AND METHODS: To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects. RESULTS: We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007). CONCLUSIONS: The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.
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Humans , Male , Apoptosis , Cell Transformation, Neoplastic , Genotype , Haplotypes , Leukemia , Lung , Lung Neoplasms , Lymphoma , Odds Ratio , Oncogenes , Phosphotransferases , Polymorphism, Single Nucleotide , Prostatic Neoplasms , Proto-OncogenesABSTRACT
Objective To study the expression of PIM-1 in prostate cancer (PCa) and its clinical significance. Methods Reverse transcription polymerase chain reaction ( RT-PCR) analysis was used to determine the expression level of PIM-1 mRNA in 2 cases of benign prostatic hyperplasia ( BPH) samples and 5 cases of PCa samples, and immunohistochemical analysis was used to investigate PIM-1 protein expression in 20 cases of BPH, 20 cases of high grade-prostatic intraepithelial neoplasia ( HGPIN) and 42 cases of PCa tissues. The immunohistochemical staining intensity was scored as negative, weak, moderate and strong positive. Results The expression level of PIM-1 mRNA in 5 cases of PCa was 0. 63 , 0. 55 , 0. 42, 0. 91 and 0. 76 ; the level in 2 cases of BPH was 0. 26 and 0. 27 , respectively. The negative rates of expression of PIM-1 protein in BPH, HGPIN and PCa tissues were 60% ( 12/20) , 20% (4/20) and 2% (1/42) ,the weak positive rates of the expression were 40% (8/12) , 20% (4/20) and 12% (5/42) , while the moderate to strong positive rates of the expression of PIM-1 protein was 0 (0/20) , 60% ( 12/20) and 86% (36/42) , respectively. Immunohistochemical analysis showed PIM-1 protein expression in PCa was higher than those in HGPIN and BPH(all P